The DPP, nationally, recruited 3,234 volunteers who received standard lifestyle recommendations and were randomly assigned to one of three interventions: intensive lifestyle with the aim of losing and maintaining 7% weight loss and achieving > 150 minutes per week of moderate intensity physical activity, metformin therapy with 850 mg twice per day, or placebo. The development of diabetes in the lifestyle intervention and metformin-treated groups were reduced by 58% and 31%, respectively, compared with the placebo group Many important issues remained unanswered, however. Specifically, whether the decrease in the development of diabetes can be sustained is unknown. Moreover, determining whether the delay or prevention of diabetes will translate into a decrease in retinopathy, nephropathy, neuropathy, and cardiovascular disease, all of which require more years to develop than the DPP period of study, is critical to establish the true impact of the DPP on public health. This long-term follow-up study of the DPP the DPPOS will address these issues. All DPP participants, whether or not they developed diabetes during the DPP, were invited to join DPPOS. 91% of the participants in the American Indian centers chose to continue in DPPOS. This was the highest percentage of any racial/ethnic group in the DPPOS. The DPPOS has continued to progress very smoothly at the American Indian sites operated by the Diabetes Epidemiology and Clinical Research Section. Retention of American Indian participants is excellent. 94% of our participants are still actively followed (defined as not having missed the last two visits), compared with 91% in the study nationally. This allows Southwestern American Indians, a population highly affected by diabetes, to participant in this major clinical trial determining long-term health benefits of diabetes prevention interventions. During the last year, the DPPOS clinical centers obtained retinal photographs of nearly all participants. This will provide an objective assessment of an important complication of diabetes diabetic retinopathy. The photographs were graded at a central reading facility and the results are currently being analyzed. We collaborate with the kidney transplantation service at the Mayo Clinic in studies of the development of new onset diabetes after transplantation, a serious complication of kidney transplantation in patients who do not have diabetes at the time of transplantation. This research may lead to clinical trials in diabetes prevention in transplant recipients.